Nanotopography induced osteogenic differentiation of human stem cells

Kingham, E.J., Tsimbouri, P.M. , Gadegaard, N. , Dalby, M.J. and Oreffo, R.O.C. (2011) Nanotopography induced osteogenic differentiation of human stem cells. Bone, 48(Sup. 2), S108-S109. (doi: 10.1016/j.bone.2011.03.177)

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Bone marrow derived skeletal stem cells and human embryonic stem cells have the capacity to maintain the stem cell state by self-renewal and the potential to differentiate to produce specialised cell types of osteogenic, adipogenic and chondrogenic lineages. The development of nanopatterned substrates as biomimetic scaffolds in combination with stem cells provides a unique approach to overcome current issues of stem cell attachment, expansion, lineage specification and directed differentiation in regenerative medicine. Using polycarbonate scaffolds with nanoscale topography (structural features of 35–120 nm in at least one dimension) of various geometries and dimensions, we have investigated the influence of nanotopography on stem cell fate in the absence of chemical induction. PCR arrays and immunofluorescence were used to investigate RNA and protein expressions and to characterise the cell types resulting from culture on defined nanotopographies. An ordered square arrangement of nanopits enhanced the expression of stem cell markers and stem cell-associated genes highlighting a potential use for in vitro expansion of skeletal stem cells prior to regenerative medical application. Conversely, increasing the disorder of nanopits in a randomly displaced square pattern induced the expression osteogenic markers in the absence of chemical osteoinductive factors. Such a pattern offers therapeutic opportunities for orthopaedic implants to improve osseointegration. To investigate a potential epigenetic mechanism for nanotopographically induced transcriptional changes, the methylation status of the osteocalcin gene promoter region was examined. The efficient production of stem cell-derived cell types will be of significant medical and research benefit. A materials approach, where nanotopography is used to expand and differentiate stem cells, will reduce the risks associated with the transplantation of differentiated cells following chemical induction and direct genetic manipulation. The current studies indicate defined nanoscale patterns can directly modulate differentiation of human stem cells and offers an innovative approach to guide osteointegration, improved healing and implant longevity in the orthopaedic environment with broad application in regenerative medicine.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Tsimbouri, Dr Monica and Dalby, Professor Matthew and Gadegaard, Professor Nikolaj
Authors: Kingham, E.J., Tsimbouri, P.M., Gadegaard, N., Dalby, M.J., and Oreffo, R.O.C.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Bone
ISSN (Online):1873-2763
Published Online:07 May 2011

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